SummaryThe packaging of genetic information into chromatin regulates a wide range of vital processes that depend on direct access to the DNA template. Many chromatin-interacting complexes impact chromatin structure and their aberrant regulation or dysfunction has been implicated in various cancers and severe developmental disorders. A better understanding of the roles of chromatin-interacting complexes in such disease states requires a detailed mechanistic study. Many chromatin-interacting complexes modify chromatin structure, yet understanding the underlying mechanisms remains a major challenge in the field. Furthermore, how chromatin-interacting complexes are regulated to enable their various functions is incompletely understood. We will address these longstanding questions in two specific aims. Aim I: Building on our expertise in single-molecule biology, we will develop powerful single-molecule imaging approaches to monitor the action of chromatin-interacting complexes in real time. We will further probe how the diverse activities of the chromatin-associated complexes are coordinated and coupled to conformational transitions. Aim II: Drawing on our expertise in structural biology, we will use a range of structural techniques in combination with biochemical approaches to study the vital regulation of chromatin-interacting complexes by their regulatory subunits as well as by chromatin features. We expect to obtain ground-breaking insights into the mechanisms and regulation of disease-related chromatin-associated complexes, which may open up new horizons for developing therapeutic intervention strategies. Furthermore, the approaches developed here will enable the investigation of a large number of chromatin-related processes.

The packaging of genetic information into chromatin regulates a wide range of vital processes that depend on direct access to the DNA template. Many chromatin-interacting complexes impact chromatin structure and their aberrant regulation or dysfunction has been implicated in various cancers and severe developmental disorders. A better understanding of the roles of chromatin-interacting complexes in such disease states requires a detailed mechanistic study. Many chromatin-interacting complexes modify chromatin structure, yet understanding the underlying mechanisms remains a major challenge in the field. Furthermore, how chromatin-interacting complexes are regulated to enable their various functions is incompletely understood. We will address these longstanding questions in two specific aims. Aim I: Building on our expertise in single-molecule biology, we will develop powerful single-molecule imaging approaches to monitor the action of chromatin-interacting complexes in real time. We will further probe how the diverse activities of the chromatin-associated complexes are coordinated and coupled to conformational transitions. Aim II: Drawing on our expertise in structural biology, we will use a range of structural techniques in combination with biochemical approaches to study the vital regulation of chromatin-interacting complexes by their regulatory subunits as well as by chromatin features. We expect to obtain ground-breaking insights into the mechanisms and regulation of disease-related chromatin-associated complexes, which may open up new horizons for developing therapeutic intervention strategies. Furthermore, the approaches developed here will enable the investigation of a large number of chromatin-related processes.

Max ERC Funding

1 498 954 €

Duration

Start date: 2017-03-01, End date: 2022-02-28

Project acronymCLIAS

ProjectMeasurement and Control of Light Fields for Application in Science and Technology

Researcher (PI)Anne L'HUILLIER

Host Institution (HI)LUNDS UNIVERSITET

Call DetailsProof of Concept (PoC), PC1, ERC-2013-PoC

Summary"Our research in attosecond science supported by the ERC advanced grant ALMA “Attosecond Control of Light and Matter”
has led us to develop a simple technique to fully characterize and control ultrashort laser electric fields. The characterization
and subsequent control can be divided into two parts:
- Measurement of the spectral phase of short light pulses by measuring second harmonic generation as a function of
dispersion introduced by e.g. a pair of glass wedges (""d-scan"" technique). From the “dispersion scans”, the spectral phase
of the pulse can be retrieved and then adjusted to perform compression of the laser pulses.
- Ultrafast measurement of the Carrier Envelope Phase offset of amplified laser pulses (""Ultrafast CEP"" technique). It is
based upon interferometry, where the second harmonic of the red edge of an octave-spanning spectrum is spectrally
interfered with the blue edge. In our implementation, the detector is a linear photodiode array and Field-Programmable Gate
Array based- electronics enables us to determine the CEP at a rate of up to 100 kHz.
The d-scan technique was invented in Lund in 2011 as a collaborative project between the University of Porto and Lund
University. An international patent application was filed on the 11th of October 2011 and published on the 18th of April 2013.
The “Ultrafast-CEP” technique was invented in Lund in 2010 and nicely complements the “d-scan” technique.
Our goal is to build a device for characterization and control of femtosecond pulses by combining both techniques and to commercialize it.
Our characterization device will be useful for the ultrafast laser community. This includes university laboratories and
research institutes in physics, chemistry, biology and medicine as well as biomedical and materials science industry."

"Our research in attosecond science supported by the ERC advanced grant ALMA “Attosecond Control of Light and Matter”
has led us to develop a simple technique to fully characterize and control ultrashort laser electric fields. The characterization
and subsequent control can be divided into two parts:
- Measurement of the spectral phase of short light pulses by measuring second harmonic generation as a function of
dispersion introduced by e.g. a pair of glass wedges (""d-scan"" technique). From the “dispersion scans”, the spectral phase
of the pulse can be retrieved and then adjusted to perform compression of the laser pulses.
- Ultrafast measurement of the Carrier Envelope Phase offset of amplified laser pulses (""Ultrafast CEP"" technique). It is
based upon interferometry, where the second harmonic of the red edge of an octave-spanning spectrum is spectrally
interfered with the blue edge. In our implementation, the detector is a linear photodiode array and Field-Programmable Gate
Array based- electronics enables us to determine the CEP at a rate of up to 100 kHz.
The d-scan technique was invented in Lund in 2011 as a collaborative project between the University of Porto and Lund
University. An international patent application was filed on the 11th of October 2011 and published on the 18th of April 2013.
The “Ultrafast-CEP” technique was invented in Lund in 2010 and nicely complements the “d-scan” technique.
Our goal is to build a device for characterization and control of femtosecond pulses by combining both techniques and to commercialize it.
Our characterization device will be useful for the ultrafast laser community. This includes university laboratories and
research institutes in physics, chemistry, biology and medicine as well as biomedical and materials science industry."

SummaryIn our ERC grant GEnetic NEtworks as a tool for anti-CAncer Drug Development we used siRNA screening and genetic
networks to identify dCTPase being involved in DNA repair and replication. Further studies revealed that dCTPase plays a
role in the degradation of nucleoside analogues used in cancer treatment. We then used an RNAi approach to validate
dCTPase as a target to improve nucleoside analogue therapy. The dCTPase protein was purified and we set up an
enzymatic high-throughput assay to screen >65,000 compounds, which generated hits that inhibit dCTPase
(IC50~1-10μM). Using in house medicinal chemistry we developed TH1217, a low nM potent and selective dCTPase
inhibitor with favourable pharmacokinetic properties. TH1217 synergistically induces apoptosis and cell death in
combination with cytidine analogue treatment in cancer cells in vitro and in vivo, but shows no increased toxicity in nontransformed
dividing cells. Here, we want to explore the commercial potential of the dCTPase inhibitors identified in the
ERC grant.
In this programme, we will, with the company Oxcia AB, establish the viability of the business programme using technical
analysis, develop a business strategy and direction, specifically secure IP, perform market analysis, develop a business
plan, manage preclinical development and prepare for clinical trials in collaboration with clinicians and regulatory bodies,
IMPD application to Medical Products Agency and identify and discuss with potential commercialization partners and
funding agencies to support cost of clinical trials. We have a non-profit foundation that owns our IP rights in an effort to
secure long term support for translational science aimed at bringing new therapies to patients. In our planned business
model, we start a new company that holds an exclusive license to the IP from the foundation which is used to develop the
overall business programme and attract investments.

In our ERC grant GEnetic NEtworks as a tool for anti-CAncer Drug Development we used siRNA screening and genetic
networks to identify dCTPase being involved in DNA repair and replication. Further studies revealed that dCTPase plays a
role in the degradation of nucleoside analogues used in cancer treatment. We then used an RNAi approach to validate
dCTPase as a target to improve nucleoside analogue therapy. The dCTPase protein was purified and we set up an
enzymatic high-throughput assay to screen >65,000 compounds, which generated hits that inhibit dCTPase
(IC50~1-10μM). Using in house medicinal chemistry we developed TH1217, a low nM potent and selective dCTPase
inhibitor with favourable pharmacokinetic properties. TH1217 synergistically induces apoptosis and cell death in
combination with cytidine analogue treatment in cancer cells in vitro and in vivo, but shows no increased toxicity in nontransformed
dividing cells. Here, we want to explore the commercial potential of the dCTPase inhibitors identified in the
ERC grant.
In this programme, we will, with the company Oxcia AB, establish the viability of the business programme using technical
analysis, develop a business strategy and direction, specifically secure IP, perform market analysis, develop a business
plan, manage preclinical development and prepare for clinical trials in collaboration with clinicians and regulatory bodies,
IMPD application to Medical Products Agency and identify and discuss with potential commercialization partners and
funding agencies to support cost of clinical trials. We have a non-profit foundation that owns our IP rights in an effort to
secure long term support for translational science aimed at bringing new therapies to patients. In our planned business
model, we start a new company that holds an exclusive license to the IP from the foundation which is used to develop the
overall business programme and attract investments.

Max ERC Funding

150 000 €

Duration

Start date: 2016-01-01, End date: 2017-06-30

Project acronymCOGOPTO

ProjectThe role of parvalbumin interneurons in cognition and behavior

Researcher (PI)Eva Marie Carlen

Host Institution (HI)KAROLINSKA INSTITUTET

Call DetailsStarting Grant (StG), LS5, ERC-2013-StG

SummaryCognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.

Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.

Max ERC Funding

1 400 000 €

Duration

Start date: 2014-02-01, End date: 2019-01-31

Project acronymcollectiveQCD

ProjectCollectivity in small, srongly interacting systems

Researcher (PI)Korinna ZAPP

Host Institution (HI)LUNDS UNIVERSITET

Call DetailsStarting Grant (StG), PE2, ERC-2018-STG

SummaryIn collisions of heavy nuclei at collider energies, for instance at the Large Hadron Collider (LHC) at CERN, the energy density is so high that an equilibrated Quark-Gluon Plasma (QGP), an exotic state of matter consisting of deconfined quarks and gluons, is formed. In proton-proton (p+p) collisions, on the other hand, the density of produced particles is low. The traditional view on such reactions is that final state particles are free and do not rescatter. This picture is challenged by recent LHC data, which found features in p+p collisions that are indicative of collective behaviour and/or the formation of a hot and dense system. These findings have been taken as signs of QGP formation in p+p reactions. Such an interpretation is complicated by the fact that jets, which are the manifestation of very energetic quarks and gluons, are quenched in heavy ion collisions, but appear to be unmodified in p+p reactions. This is puzzling because collectivity and jet quenching are caused by the same processes. So far there is no consensus about the interpretation of these results, which is also due to a lack of suitable tools.
It is the objective of this proposal to address the question whether there are collective effects in p+p collisions. To this end two models capable of describing all relevant aspects of p+p and heavy ion collisions will be developed. They will be obtained by extending a successful description of p+p to heavy ion reactions and vice versa.
The answer to these questions will either clarify the long-standing problem how collectivity emerges from fundamental interactions, or it will necessitate qualitative changes to our interpretation of collective phenomena in p+p and/or heavy ion collisions.
The PI is in a unique position to accomplish this goal, as she has spent her entire career working on different aspects of p+p and heavy ion collisions. The group in Lund is the ideal host, as it is very active in developing alternative interpretations of the data.

In collisions of heavy nuclei at collider energies, for instance at the Large Hadron Collider (LHC) at CERN, the energy density is so high that an equilibrated Quark-Gluon Plasma (QGP), an exotic state of matter consisting of deconfined quarks and gluons, is formed. In proton-proton (p+p) collisions, on the other hand, the density of produced particles is low. The traditional view on such reactions is that final state particles are free and do not rescatter. This picture is challenged by recent LHC data, which found features in p+p collisions that are indicative of collective behaviour and/or the formation of a hot and dense system. These findings have been taken as signs of QGP formation in p+p reactions. Such an interpretation is complicated by the fact that jets, which are the manifestation of very energetic quarks and gluons, are quenched in heavy ion collisions, but appear to be unmodified in p+p reactions. This is puzzling because collectivity and jet quenching are caused by the same processes. So far there is no consensus about the interpretation of these results, which is also due to a lack of suitable tools.
It is the objective of this proposal to address the question whether there are collective effects in p+p collisions. To this end two models capable of describing all relevant aspects of p+p and heavy ion collisions will be developed. They will be obtained by extending a successful description of p+p to heavy ion reactions and vice versa.
The answer to these questions will either clarify the long-standing problem how collectivity emerges from fundamental interactions, or it will necessitate qualitative changes to our interpretation of collective phenomena in p+p and/or heavy ion collisions.
The PI is in a unique position to accomplish this goal, as she has spent her entire career working on different aspects of p+p and heavy ion collisions. The group in Lund is the ideal host, as it is very active in developing alternative interpretations of the data.

SummarySelf-assembly is the key construction principle that nature uses so successfully to fabricate its molecular machinery and highly elaborate structures. In this project we will follow nature’s strategies and make a concerted experimental and theoretical effort to study, understand and control self-assembly for a new generation of colloidal building blocks. Starting point will be recent advances in colloid synthesis strategies that have led to a spectacular array of colloids of different shapes, compositions, patterns and functionalities. These allow us to investigate the influence of anisotropy in shape and interactions on aggregation and self-assembly in colloidal suspensions and mixtures. Using responsive particles we will implement colloidal lock-and-key mechanisms and then assemble a library of “colloidal molecules” with well-defined and externally tunable binding sites using microfluidics-based and externally controlled fabrication and sorting principles. We will use them to explore the equilibrium phase behavior of particle systems interacting through a finite number of binding sites. In parallel, we will exploit them and investigate colloid self-assembly into well-defined nanostructures. Here we aim at achieving much more refined control than currently possible by implementing a protein-inspired approach to controlled self-assembly. We combine molecule-like colloidal building blocks that possess directional interactions and externally triggerable specific recognition sites with directed self-assembly where external fields not only facilitate assembly, but also allow fabricating novel structures. We will use the tunable combination of different contributions to the interaction potential between the colloidal building blocks and the ability to create chirality in the assembly to establish the requirements for the controlled formation of tubular shells and thus create a colloid-based minimal model of synthetic virus capsid proteins.

Self-assembly is the key construction principle that nature uses so successfully to fabricate its molecular machinery and highly elaborate structures. In this project we will follow nature’s strategies and make a concerted experimental and theoretical effort to study, understand and control self-assembly for a new generation of colloidal building blocks. Starting point will be recent advances in colloid synthesis strategies that have led to a spectacular array of colloids of different shapes, compositions, patterns and functionalities. These allow us to investigate the influence of anisotropy in shape and interactions on aggregation and self-assembly in colloidal suspensions and mixtures. Using responsive particles we will implement colloidal lock-and-key mechanisms and then assemble a library of “colloidal molecules” with well-defined and externally tunable binding sites using microfluidics-based and externally controlled fabrication and sorting principles. We will use them to explore the equilibrium phase behavior of particle systems interacting through a finite number of binding sites. In parallel, we will exploit them and investigate colloid self-assembly into well-defined nanostructures. Here we aim at achieving much more refined control than currently possible by implementing a protein-inspired approach to controlled self-assembly. We combine molecule-like colloidal building blocks that possess directional interactions and externally triggerable specific recognition sites with directed self-assembly where external fields not only facilitate assembly, but also allow fabricating novel structures. We will use the tunable combination of different contributions to the interaction potential between the colloidal building blocks and the ability to create chirality in the assembly to establish the requirements for the controlled formation of tubular shells and thus create a colloid-based minimal model of synthetic virus capsid proteins.

Max ERC Funding

2 498 040 €

Duration

Start date: 2014-02-01, End date: 2019-01-31

Project acronymCOMPENZYMEEVOLUTION

ProjectHarnessing Proto-Enzymes for Novel Catalytic Functions

Researcher (PI)Shina Caroline Lynn Kamerlin

Host Institution (HI)UPPSALA UNIVERSITET

Call DetailsStarting Grant (StG), PE4, ERC-2012-StG_20111012

SummaryEnzymes are Nature’s catalysts, reducing the timescales of the chemical reactions that drive life from millions of years to seconds. There is also great scope for enzymes as biocatalysts outside the cell, from therapeutic and synthetic applications, to bioremediation and even for the generation of novel biofuels. Recent years have seen several impressive breakthroughs in the design of artificial enzymes, particularly through experimental studies that iteratively introduce random mutations to refine existing systems until a property of interest is observed (directed evolution), as well as examples of de novo enzyme design using combined in silico / in vitro approaches. However, the tremendous catalytic proficiencies of naturally occurring enzymes are, as yet, unmatched by any man made system, in no small part due the vastness of the sequence space that needs navigating and the almost surgical precision by which enzymatic catalysis is regulated. The proposed work aims to combine state of the art computational approaches capable of consistently reproducing the catalytic activities of both wild-type and mutant enzymes with novel screening approaches for predicting mutation hotspots, in order to redesign selected showcase systems. Specifically, we aim to (1) map catalytic promiscuity in the alkaline phosphatase superfamily, using the existing multifunctionality of these enzymes as a training set for the introduction of novel functionality, and (2) computationally design enantioselective enzymes, a problem which is of particular importance to the pharmaceutical industry due to the role of chirality in drug efficacy. The resulting theoretical constructs will be subjected to rigorous testing by our collaborators, providing a feedback loop for further design effort and methodology development. In this way, we plan to push existing theoretical tools to the limit in order to bridge the gap that exists between the catalytic proficiencies of biological and man-made catalysts.

Enzymes are Nature’s catalysts, reducing the timescales of the chemical reactions that drive life from millions of years to seconds. There is also great scope for enzymes as biocatalysts outside the cell, from therapeutic and synthetic applications, to bioremediation and even for the generation of novel biofuels. Recent years have seen several impressive breakthroughs in the design of artificial enzymes, particularly through experimental studies that iteratively introduce random mutations to refine existing systems until a property of interest is observed (directed evolution), as well as examples of de novo enzyme design using combined in silico / in vitro approaches. However, the tremendous catalytic proficiencies of naturally occurring enzymes are, as yet, unmatched by any man made system, in no small part due the vastness of the sequence space that needs navigating and the almost surgical precision by which enzymatic catalysis is regulated. The proposed work aims to combine state of the art computational approaches capable of consistently reproducing the catalytic activities of both wild-type and mutant enzymes with novel screening approaches for predicting mutation hotspots, in order to redesign selected showcase systems. Specifically, we aim to (1) map catalytic promiscuity in the alkaline phosphatase superfamily, using the existing multifunctionality of these enzymes as a training set for the introduction of novel functionality, and (2) computationally design enantioselective enzymes, a problem which is of particular importance to the pharmaceutical industry due to the role of chirality in drug efficacy. The resulting theoretical constructs will be subjected to rigorous testing by our collaborators, providing a feedback loop for further design effort and methodology development. In this way, we plan to push existing theoretical tools to the limit in order to bridge the gap that exists between the catalytic proficiencies of biological and man-made catalysts.

Max ERC Funding

1 497 667 €

Duration

Start date: 2012-10-01, End date: 2017-09-30

Project acronymComplexSex

ProjectSex-limited experimental evolution of natural and novel sex chromosomes: the role of sex in shaping complex traits

Researcher (PI)Jessica Abbott

Host Institution (HI)LUNDS UNIVERSITET

Call DetailsStarting Grant (StG), LS8, ERC-2015-STG

SummaryThe origin and evolution of sexual reproduction and sex differences represents one of the major unsolved problems in evolutionary biology, and although much progress had been made both via theory and empirical research, recent data suggest that sex chromosome evolution may be more complex than previously thought. The concept of sexual antagonism (when there is a positive intersexual genetic correlation in trait expression but opposite fitness effects of the trait(s) in males and females) has become essential to our understanding of sex chromosome evolution. The goal of this proposal is to understand how the interacting effects of sexual antagonism, sex-linked genetic variation, and sex-specific selection shape the genetic architecture of complex traits. I will test the hypotheses that: 1) individual sexually antagonistic loci are common in the genome, both in separate-sexed species and in hermaphrodites, and drive patterns of sexual antagonism often seen on the trait level. 2) That the response to sex-specific selection in sex-linked loci is usually due to standing sexually antagonistic genetic variation. 3) That sexually antagonistic variation is primarily non-additive in nature. To accomplish this, I will use a combination of approaches, including sex-limited experimental evolution of the X chromosome and reciprocal sex chromosome introgression among distantly related populations of Drosophila, quantitative genetic analysis and experimental evolution mimicking the creation of a novel sex chromosome in the hermaphroditic flatworm Macrostomum, and analytical and simulation modeling. This project will serve to confirm or refute the assumption that trait-level sexual antagonism reflects the contributions of many individual sexually antagonistic loci, increase our understanding of the contribution of coevolution of the sex chromosomes to population divergence, and help provide us with a better general understanding of how genotype maps to phenotype.

The origin and evolution of sexual reproduction and sex differences represents one of the major unsolved problems in evolutionary biology, and although much progress had been made both via theory and empirical research, recent data suggest that sex chromosome evolution may be more complex than previously thought. The concept of sexual antagonism (when there is a positive intersexual genetic correlation in trait expression but opposite fitness effects of the trait(s) in males and females) has become essential to our understanding of sex chromosome evolution. The goal of this proposal is to understand how the interacting effects of sexual antagonism, sex-linked genetic variation, and sex-specific selection shape the genetic architecture of complex traits. I will test the hypotheses that: 1) individual sexually antagonistic loci are common in the genome, both in separate-sexed species and in hermaphrodites, and drive patterns of sexual antagonism often seen on the trait level. 2) That the response to sex-specific selection in sex-linked loci is usually due to standing sexually antagonistic genetic variation. 3) That sexually antagonistic variation is primarily non-additive in nature. To accomplish this, I will use a combination of approaches, including sex-limited experimental evolution of the X chromosome and reciprocal sex chromosome introgression among distantly related populations of Drosophila, quantitative genetic analysis and experimental evolution mimicking the creation of a novel sex chromosome in the hermaphroditic flatworm Macrostomum, and analytical and simulation modeling. This project will serve to confirm or refute the assumption that trait-level sexual antagonism reflects the contributions of many individual sexually antagonistic loci, increase our understanding of the contribution of coevolution of the sex chromosomes to population divergence, and help provide us with a better general understanding of how genotype maps to phenotype.

Max ERC Funding

1 492 011 €

Duration

Start date: 2016-05-01, End date: 2021-04-30

Project acronymComplexSwimmers

ProjectBiocompatible and Interactive Artificial Micro- and Nanoswimmers and Their Applications

Researcher (PI)Giovanni Volpe

Host Institution (HI)GOETEBORGS UNIVERSITET

Call DetailsStarting Grant (StG), PE4, ERC-2015-STG

SummaryMicroswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing.
However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale.
This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers.
To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.

Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing.
However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale.
This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers.
To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.

Max ERC Funding

1 497 500 €

Duration

Start date: 2016-09-01, End date: 2021-08-31

Project acronymCONPOL

ProjectContexts, networks and participation: The social logic of political engagement

Researcher (PI)Sven Aron Oskarsson

Host Institution (HI)UPPSALA UNIVERSITET

Call DetailsConsolidator Grant (CoG), SH2, ERC-2015-CoG

SummaryThe statement that individuals’ immediate social circumstances influence how they think and act in the political sphere is a truism. However, both theoretical and empirical considerations have often prevented political scientists from incorporating this logic into analyses of political behavior. In the CONPOL project we argue that it is necessary to return to the idea that politics follows a social logic in order to push the theoretical and empirical boundaries in explaining political behavior. That is, people do not act as isolated individuals when confronting complex political tasks such as deciding whether to vote and which party or candidate to vote for. Instead politics should be seen as a social experience in which individuals arrive at their decisions within particular social settings: the family, the peer group, the workplace, the neighborhood. In what way do parents and other family members influence an individual’s political choices? What is the role of workmates and neighbors when individuals arrive at political decisions? Do friends and friends’ friends affect how you think and act in the political sphere? To answer such questions the standard approach to gather empirical evidence on political behavior based on national sample surveys needs to be complemented by the use of population wide register data. The empirical core of the CONPOL project is unique Swedish register data. Via the population registers provided by Statistics Sweden it is possible to identify several relevant social settings such as parent-child relations and the location of individuals within workplaces and neighborhoods. The registers also allow us to identify certain network links between individuals. Furthermore, Statistics Sweden holds information on several variables measuring important political traits. A major aim for CONPOL is to complement this information by scanning in and digitalizing election rolls with individual-level information on turnout across several elections.

The statement that individuals’ immediate social circumstances influence how they think and act in the political sphere is a truism. However, both theoretical and empirical considerations have often prevented political scientists from incorporating this logic into analyses of political behavior. In the CONPOL project we argue that it is necessary to return to the idea that politics follows a social logic in order to push the theoretical and empirical boundaries in explaining political behavior. That is, people do not act as isolated individuals when confronting complex political tasks such as deciding whether to vote and which party or candidate to vote for. Instead politics should be seen as a social experience in which individuals arrive at their decisions within particular social settings: the family, the peer group, the workplace, the neighborhood. In what way do parents and other family members influence an individual’s political choices? What is the role of workmates and neighbors when individuals arrive at political decisions? Do friends and friends’ friends affect how you think and act in the political sphere? To answer such questions the standard approach to gather empirical evidence on political behavior based on national sample surveys needs to be complemented by the use of population wide register data. The empirical core of the CONPOL project is unique Swedish register data. Via the population registers provided by Statistics Sweden it is possible to identify several relevant social settings such as parent-child relations and the location of individuals within workplaces and neighborhoods. The registers also allow us to identify certain network links between individuals. Furthermore, Statistics Sweden holds information on several variables measuring important political traits. A major aim for CONPOL is to complement this information by scanning in and digitalizing election rolls with individual-level information on turnout across several elections.